CA2336445A1 - Glycopeptide derivatives and pharmaceutical compositions containing the same - Google Patents

Glycopeptide derivatives and pharmaceutical compositions containing the same Download PDF

Info

Publication number
CA2336445A1
CA2336445A1 CA002336445A CA2336445A CA2336445A1 CA 2336445 A1 CA2336445 A1 CA 2336445A1 CA 002336445 A CA002336445 A CA 002336445A CA 2336445 A CA2336445 A CA 2336445A CA 2336445 A1 CA2336445 A1 CA 2336445A1
Authority
CA
Canada
Prior art keywords
substituted
hydrogen
ch2ch2
group
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002336445A
Other languages
French (fr)
Other versions
CA2336445C (en
Inventor
J. Kevin Judice
Paul Ross Fatheree
Bernice M. T. Lam
Michael Leadbetter
Martin Sheringham Linsell
Yongqi Mu
Sean Gary Trapp
Guang Yang
Yan Zhu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cumberland Pharmaceuticals Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2336445A1 publication Critical patent/CA2336445A1/en
Application granted granted Critical
Publication of CA2336445C publication Critical patent/CA2336445C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K9/00Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K9/00Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
    • C07K9/006Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
    • C07K9/008Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oncology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed are derivatives of glycopeptide compounds having at least one substituent of the formula: -Ra-Y-Rb-(Z)x where Ra, Rb, Y, Z and x are as defined, and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.

Claims (71)

1. A glycopeptide compound having at least one substituent of the formula:
-R a-Y-R b-(Z)x wherein each R a is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
each R b is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided R b is not a covalent bond when Z
is hydrogen;
each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-, -NR c-, -S(O)-, -SO2-, -NR c C(O)-, -OC(O)-, -NR c SO2-, -OSO2-, -C(O)NR c-, -C(O)O-, -SO2NR c-, -SO2O-, ,-P(O)(OR c)O-, -P(O)(OR c)NR c-, -OP(O)(OR c)O-,-OP(O)(OR c)NR c-, -OC(O)O-, -NR c C(O)O-, -NR c C(O)NR c-, -OC(O)NR c- and -NR c SO2NR c-;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
each R c is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -C(O)R d;
each R d is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
x is 1 or 2;
and pharmaceutically acceptable salts thereof;
provided that:
(i) when Y is -NR c- , R c is alkyl of 1 to 4 carbon atoms, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(ii) when Y is -C(O)NR c-, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(iii) when Y is sulfur, Z is hydrogen and R b is alkylene, then R b contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and R b is alkylene, then R b contains at least 11 carbon atoms.
2. The compound of Claim 1, wherein the glycopeptide compound is substituted with from 1 to 3 substituents of the formula -R a-Y-R b-(Z)x.
3. The compound of Claim 2, wherein each R a is independently selected from alkylene having from 1 to 10 carbon atoms.
4. The compound of Claim 3, wherein R a is ethylene or propylene.
5. The compound of Claim 2, wherein Z is hydrogen and R b is alkylene of from 8 to 12 carbon atoms.
6. The compound of Claim 5, wherein R b and Z form an n-actyl, n-nonyl, n-decyl, n-undecyl or n-dodecyl group.
7. The compound of Claim 2, wherein Z is aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocyclic and R b is a covalent bond or alkylene of from 1 to 10 carbon atoms.
8. The compound of Claim 7, wherein Z is aryl and R b is a covalent bond, methylene, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9- or -(CH2)10-.
9. The compound of Claim 2, wherein each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-, -NR c- , -S(O)-, -SO2-, -NR c C(O)-, -OC(O)-, -NR c SO2-, -C(O)NR c-, -C(O)O- and -SO2NR c-.
10. The compound of Claim 9, wherein Y is oxygen, sulfur, -NR c- or -NR c SO2-.
11. The compound of Claim 2, wherein each Z is independently selected from hydrogen, aryl, cycloalkyl, heteroaryl and heterocyclic.
12. The compound of Claim 11, wherein Z is hydrogen or aryl.
13. The compound of Claim 12, wherein Z is phenyl, substituted phenyl, biphenyl, substituted biphenyl or terphenyl.
14. The compound of Claim 2, wherein the -R a-Y-R b-(Z)x group is selected from the group consisting of:
-CH2CH2-NH-(CH2)9CH3;
-CH2CH2CH2-NH-(CH2)8CH3;
-CH2CH2CH2CH2-NH-(CH2)7CH3;
-CH2CH2-NHSO2-(CH2)9CH3;

-CH2CH2-NHSO2-(CH2)11CH3;
-CH2CH2-S-(CH2)8CH3;
-CH2CH2-S-(CH2)9CH3;
-CH2CH2-S-(CH2)10CH3;
-CH2CH2CH2-S-(CH2)8CH3;
-CH2CH2CH2-S-(CH2)9CH3;
-CH2CH2CH2-S-(CH2)3-CH=CH-(CH2)4CH3 (trans);
-CH2CH2CH2CH2-S-(CH2)7CH3;
-CH2CH2-S(O)-(CH2)9CH3;
-CH2CH2-S-(CH2)6Ph;
-CH2CH2-S-(CH2)8Ph;
-CH2CH2CH2-S-(CH2)8Ph:
-CH2CH2-NH-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-NH-CH2-4-[4-CH3)2CHCH2-]-Ph;
-CH2CH2-NH-CH2-4-(4-CF3-Ph)-Ph;
-CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-[3,4-di-Cl-PhCH2O-)-Ph;
-CH2CH2-NHSO2-CH2-4-[4-(4-Ph)-Ph]-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(Ph-C~C-)-Ph;
-CH2CH2CH2-NHSO2-4-(4-Cl-Ph)-Ph; and -CH2CH2CH2-NHSO2-4-(naphth-2-yl)-Ph.
15. A compound of formula I:

wherein R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -R a-Y-R b-(Z)x; or a saccharide group optionally substituted with -R a-Y-R b(Z)x;
R2 is hydrogen or a saccharide group optionally substituted with -R a-Y-R b-(Z)x:
R' is -OR c, -NR c R c, -O-R a-Y-R b-(Z)x, -NR c-R a-Y-R b-(Z)x, -NR c R c, or -O-R c ;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, -R a-Y-R b-(Z)x, -C(O)R d and a saccharide group optionally substituted with -R a-Y-R b-(Z)x;

R5 is selected from the group consisting of hydrogen, halo, -CH(R c)-NR c R c, -CH(R c)-NR c R c and -CH(R c)-NR c-R a-Y-R b-(Z)x;
R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, -R a-Y-R b-(Z)x, -C(O)R d and a saccharide group optionally substituted with -NR c-R a-Y-R b-(Z)x, or R5 and R6 can be joined, together with the atoms to which they are attached, form a heterocyclic ring optionally substituted with -NR c-R a-Y-R b-(Z)x;
R7is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl,-R a-Y-R b-(Z)x, and -C(O)R d;
R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R9 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R10 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; or R8 and R10 are joined to form -Ar1-O-Ar2-, where Ar1 and Ar2 are independently arylene or heteroarylene;
R11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic, or R10 and R11 are joined, together with the carbon and nitrogen atoms to which they are attached, to form a heterocyclic ring;

R12 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, -C(O)R d, -C(NH)R d, -C(O)NR c R c, -C(O)OR d, -C(NH)NR c R c and -R a-Y-R b-(Z)x, or R11 and R12 are joined, together with the nitrogen atom to which they are attached, to form a heterocyclic ring;
R13 is selected from the group consisting of hydrogen or -OR14;
R14 is selected from hydrogen, -C(O)R d and a saccharide group;
each R a is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
each R b is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided R b is not a covalent bond when Z
is hydrogen;
each R c is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -C(O)R d;
each R d is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R c is a saccharide group;
X1, X2 and X3 are independently selected from hydrogen or chloro;
each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-, -NR c-, -S(O}-, -SO2-, -NR c C(O)-, -OSO2-, -OC(O)-, -NR c SO2-, -C(O)NR c-, -C(O)O-, -SO2NR c- , -SO2O-, -P(O)(OR c}O-, -P(O)(OR c)NR c-, -OP(O)(OR c)O-,-OP(O)(OR c)NR c-, -OC(O)O-, -NR c C(O)O-, -NR c C(O)NR c-, -OC(O)NR c- and -NR c SO2NR c-;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
n is 0, 1 or 2;
x is 1 or 2;
and pharmaceutically acceptable salts, stereoisomers and prodrugs thereof;
provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R12 has a substitutent of the formula -R a-Y-R b-(Z)x;
and further provided that:
(i) when Y is -NR c-, R b is alkyl of 1 to 4 carbon atoms, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(ii) when Y is -C(O)NR c-, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(iii) when Y is sulfur, Z is hydrogen and R b is alkylene, then R b contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and R b is alkylene, then R b contains at least 11 carbon atoms.
16. The compound of Claim 15, wherein R1 is a saccharide group optionally substituted with -R a-Y-R b-(Z)x.
17. The compound of Claim 16, wherein R1 is a saccharide group of the formula:

wherein R15 is -R a-Y-R b-(Z)x; and R16 is hydrogen or methyl.
18. The compound of Claim 17, wherein R15 is a -R a-Y-R b-(Z)x group selected from the group consisting of:
- CH2CH2-NH-(CH2)9CH3;
-CH2CH2CH2-NH-(CH2)8CH3;
-CH2CH2CH2CH2-NH-(CH2)7CH3;
-CH2CH2-NHSO2-(CH2)9CH3;
-CH2CH2-NHSO2-(CH2)11CH3;
-CH2CH2-S-(CH2)8CH3;
-CH2CH2-S-(CH2)9CH3;
-CH2CH2-S-(CH2)10CH3;
-CH2CH2CH2-S-(CH2)8CH3;
-CH2CH2CH2-S-(CH2)9CH3;
-CH2CH2CH2-S-(CH2)3-CH=CH-(CH2)4CH3 (trans);
-CH2CH2CH2CH2-S-(CH2)7CH3;
-CH2CH2-S(O)-(CH2)9CH3;
-CH2CH2-S-(CH2)6Ph;

-CH2CH2-S-(CH2)8Ph;
-CH2CH2CH2-S-(CH2)8Ph;
-CH2CH2-NH-(NH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-NH-(NH2-4-[4-CH3)2CHCH2-]-Ph;
-CH2CH2-NH-CH2-4-(4-CF3-Ph)-Ph;
-CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S- CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-[3,4-di-Cl-PhCH2O-)-Ph;
-CH2CH2-NHSO2-CH2-4-[4-(4-Ph)-Ph]-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(Ph-C~C-)-Ph;
-CH2CH2CH2-NHSO2-4-(4-Cl-Ph)-Ph; and -CH2CH2CH2-NHSO2-4-(naphth-2-yl)-Ph.
19. The compound of Claim 15, wherein R3 is -OH or -NR c R c.
20. The compound of Claim 15, wherein R5 is hydrogen, -CH2-N-(N-CH3-D-glucamine); -CH2-NH-CH2CH2-NH-(CH2)9CH3; -CH2-NH-CH2CH2-NH-(CH2)11CH3; -CH2-NH-(CH2)5-COOH; and -CH2-N (2-amino-2-deoxygluconic acid).
21. The compound of Claim 15, wherein R8 is -CH2C(O)NH2, -CH2COOH, benzyl, 4-hydroxyphenyl or 3-chloro-4-hydroxyphenyl.
22. The compound of Claim 15, wherein R9 is hydrogen and R11 is hydrogen or methyl.
23. The compound of Claim 22, wherein R10 is alkyl or substituted alkyl.
24. The compound of Claim 23, wherein R12 is hydrogen, alkyl, substituted alkyl or -C(O)R d.
25. The compound of Claim 24, wherein n is 1.
26. A compound of formula II:
wherein R21 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -R a-Y-R b-(Z)x; or a saccharide group optionally substituted with -R a-Y-R b-(Z)x;

R22 is -ORc, -NRcRc, -O-Ra-Y-Rb-(Z)x or -NRc-Ra-Y-Rb-(Z)x;
R23 is selected from the group consisting of hydrogen, halo, -CH(Rc)-NRcRc, -CH(Rc)-Re and -CH(Rc)-NRc-Ra-Y-Rb-(Z)x;
R24 is selected from the group consisting of hydrogen and lower alkyl;
R25 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R26 is selected from the group consisting of hydrogen and lower alkyl; or R25 and R26 are joined, together with the carbon and nitrogen atoms to which they are attached, to form a heterocyclic ring;
R27 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, -C(O)Rd,-C(NH)Rd, -C(O)NRcRc, -C(O)ORd,-C(NH)NRcRc and -Ra-Y-Rb-(Z)x, or R26 and R27 are joined, together with the nitrogen atom to which they are attached, to form a heterocyclic ring;
each Ra is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
each Rb is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided Rb is not a covalent bond when Z
is hydrogen;
each Rc is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -C(O)Rd;

each Rd is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
Re is an aminosaccharide group;
each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-,-NRc-, -S(O)-, -SO2-, -NRcC(O)-, -OSO2-, -OC(O)-, -NRcSO2-, -C(O)NRc-, -C(O)O-, -SO2NRc-, -SO2O-, -P(O)(ORc)O-, -P(O)(ORc)NRc-, -OP(O)(ORc)O-,-OP(O)(ORc)NRc-, -OC(O)O-, -NRcC(O)O-, -NRcC(O)NRc-, -OC(O)NRc- and -NRcSO2NRc-;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
n is 0, 1 or 2;
x is 1 or 2;
and pharmaceutically acceptable salts, stereoisomers and prodrugs thereof;
provided that at least one of R21, R22, R23 or R27 has a substitutent of the formula -Ra-Y-Rb-(Z)x;
and further provided that:
(i) when Y is-NRc-, Rc is alkyl of 1 to 4 carbon atoms, Z is hydrogen and Rb is alkylene, then Rb contains at least 5 carbon atoms;
(ii) when Y is -C(O)NRc-, Z is hydrogen and Rb is alkylene, then Rb contains at least 5 carbon atoms;
(iii) when Y is sulfur, Z is hydrogen and Rb is alkylene, then Rb contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and Rb is alkylene, then Rb contains at least 11 carbon atoms.
27. The compound of Claim 26, wherein R21 is a saccharide group of the formula:

wherein R15 is - Ra- Y- Rb- (Z)x, and R16 is hydrogen or methyl.
28. The compound of Claim 27, wherein R15 is a -Ra-Y-Rb-(Z)x group selected from the group consisting of:
-CH2CH2- NH- (CH2)9CH3;
-CH2CH2CH2-NH-(CH2)8CH3;
-CH2CH2CH2CH2-NH-(CH2)7CH3;
-CH2CH2-NHSO2-(CH2)9CH3;
-CH2CH2- NHSO2-(CH2)11CH3;
-CH2CH2-S-(CH2)8CH3;
-CH2CH2-S-(CH2)9CH3;
-CH2CH2-S-(CH2)10CH3;
-CH2CH2CH2-S-(CH2)8CH3;
-CH2CH2CH2-S-(CH2)9CH3;
-CH2CH2CH2-S-(CH2)3-CH=CH-(CH2)4CH3 (trans);
-CH2CH2CH2CH2-S-(CH2)7CH3;
- CH2CH2-S(O)-(CH2)9CH3;
-CH2CH2-S-(CH2)6Ph;
-CH2CH2-S-(CH2)8Ph;

-CH2CH2CH2-S-(CH2)8Ph;
-CH2CH2-NH-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-NH-CH2-4-[4-CH3)2CHCH2-]-Ph;
-CH2CH2-NH-CH2-4-(4-CF3-Ph)-Ph;
- CH2CH2-S-CH2-4-(4Cl-Ph)-Ph -CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
- CH2CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
- CH2CH2CH2-S-CH2-4-[3,4-di-Cl-PhCH2O-)-Ph;
- CH2CH2-NHSO2-CH2-4-[4-(4Ph)-Ph]-Ph - CH2CH2CH2-NHSO2-CH2-4-(4-Cl-Ph)-Ph;
- CH2CH2CH2-NHSO2-CH2-4-(Ph-C~C-)-Ph;
-CH2CH2CH2-NHSO2-4-(4-Cl-Ph)-Ph; and -CH2CH2CH2-NHSO2-4-(naphth-2-yl)-Ph.
29. The compound of Claim 26, wherein R22 is -OH or -NRcRc.
30. The compound of Claim 26, wherein R23 is hydrogen, -CH2-N-(N-CH3-D-glucamine); -CH2-NH-CH2CH2-NH-(CH2)9CH3; -CH2-NH-CH2CH2-NH-(CH2)11,CH3;-CH2-NH-(CH2)5-COOH; or -CH2-N (2-amino-2-deoxygluconic acid).
31. The compound of Claim 26, wherein R24 is hydrogen and R26 is hydrogen or methyl.
32. The compound of Claim 31, wherein R25 is alkyl or substituted alkyl.
33. The compound of Claim 32, wherein R25 is isobutyl.
34. The compound of Claim 33, wherein R27 is hydrogen, alkyl, substituted alkyl or -C(O)Rd.
35. A compound shown in any of Tables I, II, III, IV, V or VI, or a pharmaceutically-acceptable salt thereof.
36. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically effective amount of a glycopeptide compound having at least one substituent of the formula:
-Ra-Y-Rb-(Z)x wherein each Ra is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
each Rb is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided Rb is not a covalent bond when Z
is hydrogen;
each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-, -NRc-, -S(O)-, -SO2-, -NRcC(O)-, -OC(O)-, -NRcSO2-, -OSO2-, -C(O)NRc-, -C(O)O-, -SO2NRc-, -SO2O-, ,-P(O)(ORc)O-, -P(O)(ORc)NRc-, -OP(O)(ORc)O-,-OP(O)(ORc)NRc-, -OC(O)O-, -NRcC(O)O-, -NRcC(O)NRc-, -OC(O)NRc- and -NRcSO2NRc-;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
each Rc is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -C(O)R ;
each R d is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
x is 1 or 2;
and pharmaceutically acceptable salts thereof;
provided that:
(i) when Y is -NR c-, R c is alkyl of 1 to 4 carbon atoms, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(ii) when Y is -C(O)NR c-,Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(iii) when Y is sulfur, Z is hydrogen and R b is alkylene, then R b contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and R b is alkylene, then R b contains at least 11 carbon atoms.
37. The pharmaceutical composition of Claim 36, wherein the glycopeptide compound is substituted with from 1 to 3 substituents of the formula -R a-Y-R b-(Z)x.
38. The pharmaceutical composition of Claim 37, wherein each R a is independently selected from alkylene having from 1 to 10 carbon atoms.
39. The pharmaceutical composition of Claim 38, wherein R a is ethylene or propylene.
40. The pharmaceutical composition of Claim 37, wherein Z is hydrogen and Rb is alkylene of from 8 to 12 carbon atoms.
41. The pharmaceutical composition of Claim 40, wherein Rb and Z
form an n-octyl, n-nonyl, n-decyl, n-undecyl or n-dodecyl group.
42. The pharmaceutical composition of Claim 37, wherein Z is aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocyclic and Rb is a covalent bond or alkylene of from 1 to 10 carbon atoms.
43. The pharmaceutical composition of Claim 42, wherein Z is aryl and Rb is a covalent bond, methylene, -(CH2)6-, -(CH2)7-,-(CH2)8-,-(CH2)9-or -(CH2)10-.
44. The pharmaceutical composition of Claim 37, wherein each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-, -NRc-, -S(O)-, -SO2-, -NRcC(O)-, -OC(O)-, -NRcSO2-, -C(O)NRc-, -C(O)O- and - SO2NRc- .
45. The pharmaceutical composition of Claim 44, wherein Y is oxygen, sulfur, -NRc- or -NRcSO2-
46. The pharmaceutical composition of Claim 37, wherein each Z is independently selected from hydrogen, aryl, cycloalkyl, heteroaryl and heterocyclic.
47. The pharmaceutical composition of Claim 46, wherein Z is hydrogen or aryl.
48. The pharmaceutical composition of Claim 47, wherein Z is phenyl, substituted phenyl, biphenyl, substituted biphenyl or terphenyl.
49. The pharmaceutical composition of Claim 37, wherein the -Ra-Y-Rb-(Z)x group is selected from the group consisting of:
-CH2CH2- NH- {CH2)9CH3;
-CH2CH2CH2-NH-(CH2)8CH3;
- CH2CH2CH2CH2- NH- (CH2)7CH3;
- CH2CH2- NHSO2-(CH2)9CH3;
-CH2CH2-NHSO2-(CH2)11CH3;
-CH2CH2-S-(CH2)8CH3;
- CH2CH2-S-{CH2)9CH3;
- CH2CH2-S-(CH2}10CH3;
- CH2CH2CH2-S- {CH2)8CH3;
- CH2CH2CH2-S-{CH2}9CH3;
-CH2CH2CH2-S-{CH2)3-CH=CH-(CH2)4CH3 (trans);
- CH2CH2CH2CH2-S-(CH2)7CH3;
-CH2CH2-S(O)-(CH2)9CH3;
-CH2CH2-S-(CH2)6Ph;
-CH2CH2-S-(CH2)8Ph;
- CH2CH2CH2-S-(CH2)8Ph;
-CH2CH2-NH-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-NH-CH2-4-[4-CH3)2CHCH2-]-Ph;
- CH2CH2-NH-CH2-4-(4-CF3-Ph}-Ph;
- CH2CH2- S- CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2- S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-[3,4-di-Cl-PhCH2O-)-Ph;

- CH2CH2- NHSO2- CH2-4-[4-(4-Ph)-Ph]-Ph;
-CH2CH2CH2- NHSO2-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2- NHSO2-CH2-4-(Ph-C~C-)-Ph;
-CH2CH2CH2-NHSO2-4-(4-Cl-Ph)-Ph; and -CH2CH2CH2- NHSO2-4-(naphth-2-yl)-Ph.
50. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically effective amount of a compound of formula I:
wherein R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -Ra-Y-Rb-(Z)x; or a saccharide group optionally substituted with - Ra- Y- Rb- (Z)x;

R2 is hydrogen or a saccharide group optionally substituted with - Ra-Y-Rb-(Z)x;
R3 is - ORc, - NRcRc, -O- Ra- Y- Rb- (Z)x, -NRc- Ra- Y- Rb- (Z)x, -NRcRc, or -O-Re;
R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, -Ra-Y-Rb-(Z)x, -C(O)Rd and a saccharide group optionally substituted with -Ra-Y-Rb-(Z)x;
R5 is selected from the group consisting of hydrogen, halo, -CH(Rc)-NRcRc, -CH(Rc)-NRcRc and -CH(Rc)-NRc-Ra-Y-Rb-(Z)x;
R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, -Ra-Y-Rb-(Z)x, -C(O)Rd and a saccharide group optionally substituted with -NRc-Ra-Y-Rb-(Z)x, or R5 and R6 can be joined, together with the atoms to which they are attached, form a heterocyclic ring optionally substituted with -NRc-Ra-Y-Rb-(Z)x;
R7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl,-Ra-Y-Rb-(Z)x, and -C(O)Rd;
R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R9 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R10 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; or R8 and R10 are joined to form -Ar1-O-Ar2-, where Ar1 and Ar2 are independently arylene or heteroarylene;
R11" is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic, or R10 and R11 are joined, together with the carbon and nitrogen atoms to which they are attached, to form a heterocyclic ring;
R12 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, -C(O)Rd, --C(NH)Rd, -C(O)NRcRc, -C(O)ORd, -C(NH)NRcRc and -Ra-Y-Rb-(Z)x, or R11 and R12 are joined, together with the nitrogen atom to which they are attached, to form a heterocyclic ring;
R13 is selected from the group consisting of hydrogen or -OR14;
R14 is selected from hydrogen, -C(O)Rd and a saccharide group;
each Ra is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
each Rb is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided Rb is not a covalent bond when Z
is hydrogen;
each Rc is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -C(O)Rd;
each Rd is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
Rc is a saccharide group;
X1, X2 and X3 are independently selected from hydrogen or chloro;
each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-, -NRc-, -S(O)-, -SO2-, -NRcC(O)-, -OSO2-, -OC(O)-, - NRcSO2- , - C(O)NRc- , -C(O)O- , - SO2NRc- , - SO2O- , -P(O)(ORc)O- , -P(O)(ORc)NRc-, -OP(O)(ORc)O-,-OP(O)(ORc)NRc-, -OC(O)O-, -NRcC(O)O-, -NRcC(O)NRc-, -OC(O)NRc- and -NRcSO2NRc-;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
n is 0, 1 or 2;
x is 1 or 2;
and pharmaceutically acceptable salts, stereoisomers and prodrugs thereof;
provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R12 has a substitutent of the formula -Ra-Y-Rb-(Z)x;
and further provided that:
(i) when Y is -NRc-, Rc is alkyl of 1 to 4 carbon atoms, Z is hydrogen and Rb is alkylene, then Rb contains at least 5 carbon atoms;
(ii) when Y is -C(O)NRc-, Z is hydrogen and Rb is alkylene, then Rb contains at least 5 carbon atoms;
(iii) when Y is sulfur, Z is hydrogen and Rb is alkylene, then Rb contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and Rb is alkylene, then Rb contains at least 11 carbon atoms.
51. The pharmaceutical composition of Claim 50, wherein R1 is a saccharide group optionally substituted with -Ra-Y-Rb-(Z)x.
52. The pharmaceutical composition of Claim 51, wherein R1 is a saccharide group of the formula:
wherein R15 is -Ra-Y-Rb-(Z)x; and R16 is hydrogen or methyl.
53. The pharmaceutical composition of Claim 52, wherein R15 is a -Ra-Y-Rb-(Z)x group selected from the group consisting of:
- CH2CH2- NH- (CH2)9CH3;
- CH2CH2CH2- NH- (CH2)8CH3;
- CH2CH2CH2CH2- NH- (CH2)7CH3;
- CH2CH2- NHSO2- (CH2)9CH3;
- CH2CH2- NHSO2- (CH2)11CH3;
-CH2CH2-S-(CH2)8CH3;
-CH2CH2-S-(CH2)9CH3;
-CH2CH2-S-(CH2)10CH3;
-CH2CH2CH2-S-(CH2)8CH3;
-CH2CH2CH2-S-(CH2)9CH3;
-CH2CH2CH2-S-(CH2)3-CH=CH-(CH2)4CH3 (trans);
-CH2CH2CH2CH2-S-(CH2)7CH3;

-CH2CH2-S(O)-(CH2)9CH3;
-CH2CH2-S-(CH2)6Ph;
-CH2CH2-S-(CH2)8Ph;
-CH2CH2CH2-S-(CH2)8Ph;
-CH2CH2-NH-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-NH-CH2-4-[4-CH3)2CHCH2-]-Ph;
-CH2CH2-NH-CH2-4-(4-CF3-Ph)-Ph;
-CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-[3,4-di-Cl-PhCH2O-)-Ph;
-CH2CH2-NHSO2-CH2-4-[4-(4-Ph)-Ph]-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(Ph-C~C-)-Ph;
-CH2CH2CH2-NHSO2-4-(4-Cl-Ph)-Ph; and -CH2CH2CH2-NHSO2-4-(naphth-2-yl)-Ph.
54. The pharmaceutical composition of Claim 50, wherein R3 is -OH or -NR c R c.
55. The pharmaceutical composition of Claim 50, wherein R5 is hydrogen, -CH2-N-(N-CH3-D-glucamine); -CH2-NH-CH2CH2-NH-(CH2)9CH3;-CH2-NH-CH2CH2-NH-(CH2)11CH3; -CH2-NH-(CH2)5-COOH; and -CH2-N-(2-amino-2-deoxygluconic acid).
56. The pharmaceutical composition of Claim 50, wherein R8 is -CH2C(O)NH2, -CH2COOH, benzyl, 4-hydroxyphenyl or 3-chloro-4-hydroxyphenyl.
57. The pharmaceutical composition of Claim 50, wherein R9 is hydrogen and R11 is hydrogen or methyl.
58. The pharmaceutical composition of Claim 57, wherein R10 is alkyl or substituted alkyl.
59. The pharmaceutical composition of Claim 58, wherein R12 is hydrogen, alkyl, substituted alkyl or -C(O)R d.
60. The pharmaceutical composition of Claim 50, wherein n is 1.
61. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically effective amount of a compound of formula II:
wherein R21 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -R a-Y-R b-(Z)x; or a saccharide group optionally substituted with -R a-Y-R b-(Z)x;
R22 is -OR c, -NR c R c, -O-R a-Y-R b-(Z)x or -NR c-R a-Y-R b-(Z)x;
R23 is selected from the group consisting of hydrogen, halo, -CH(R c)-NR c R c, -CH(R c)-R e and -CH(R c)-NR c-R a-Y-R b-(Z)x;
R24 is selected from the group consisting of hydrogen and lower alkyl;
R25 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R26 is selected from the group consisting of hydrogen and lower alkyl; or R25 and R26 are joined, together with the carbon and nitrogen atoms to which they are attached, to form a heterocyclic ring;
R27 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, -C(O)R d, -C(NH)R d, -C(O)NR c R c, -C(O)OR d, -C(NH)NR c R c and -R a-Y-R b-(Z)x, or R26 and R27 are joined, together with the nitrogen atom to which they are attached, to form a heterocyclic ring;
each R a is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
each R b is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided R b is not a covalent bond when Z
is hydrogen;

each R c is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and -C(O)R d;
each R d is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
R c is an aminosaccharide group;
each Y is independently selected from the group consisting of oxygen, sulfur, -S-S-,-NR c-, -S(O)-, -SO2-, -NR c C(O)-, -OSO2-, -OC(O)-, -NR c SO2-, -C(O)NR c-, -C(O)O-, -SO2NR c-, -SO2O-, -P(O)(OR c)O-, -P(O)(OR c)NR c-, -OP(O)(OR c)O-,-OP(O)(OR c)NR c-, -OC(O)O-, -NR c C(O)O-, -NR c C(O)NR c-, -OC(O)NR c- and -NR c SO2NR c-;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
n is 0, 1 or 2;
x is 1 or 2;
and pharmaceutically acceptable salts, stereoisomers and prodrugs thereof;
provided that at least one of R21, R22, R22 or R27 has a substitutent of the formula -R a-Y-R b-(Z)x;
and further provided that:
(i) when Y is -NR c-, R c is alkyl of 1 to 4 carbon atoms, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(ii) when Y is -C(O)NR c-, Z is hydrogen and R b is alkylene, then R b contains at least 5 carbon atoms;
(iii) when Y is sulfur, Z is hydrogen and R b is alkylene, then R b contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and Rb is alkylene, then Rh contains at least 11 carbon atoms.
62. The pharmaceutical composition of Claim 61, wherein R21 is a saccharide group of the formula:

wherein R15 is -Ra-Y-Rb--(Z)x, and R16 is hydrogen or methyl.
63. The pharmaceutical composition of Claim 62, wherein R15 is a -Ra-Y-Rb-(Z)x group selected from the group consisting of:
-CH2CH2-NH-(CH2)9CH3;
-CH2CH2CH2- NH-(CH2)8CH3;
-CH2CH2CH2CH2- NH- (CH2),CH3;
-CH2CH2-NHSO2-(CH2)9CH3;
-CH2CH2-NHSO2-(CH2)11CH3;
-CH2CH2-S-(CH2)8CH3;
-CH2CH2-S-(CH2)9CH3;
-CH2CH2-S-(CH2)10CH3, -CH2CH2CH2-S-(CH2)8CH3;

-CH2CH2CH2-S-(CH2)9CH3;
-CH2CH2CH2-S-(CH2)3-CH=CH-(CH2)4CH3 (trans);
-CH2CH2CH2CH2-S-(CH2),CH3;
-CH2CH2-S(O)-(CH2)9CH3;
-CH2CH2-S-(CH2)6Ph;
-CH2CH2-S-(CH2)8Ph;
-CH2CH2CH2-S-(CH2)8Ph;
-CH2CH2-NH-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-NH-CH2-4-[4-CH3)2CHCH2-]-Ph;
-CH2CH2-NH-CH2-4-(4-CF3-Ph)-Ph;
-CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S(O)-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-S-CH2-4-[3,4-di-Cl-PhCH2O-)-Ph;
-CH2CH2-NHSO2-CH2-4-[4-(4-Ph)-Ph]-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(4-Cl-Ph)-Ph;
-CH2CH2CH2-NHSO2-CH2-4-(Ph-C~C-)-Ph;
-CH2CH2CH2-NHSO2-4-(4-Cl-Ph)-Ph; and -CH2CH2CH2-NHSO2-4-(naphth-2-yl)-Ph.
64. The pharmaceutical composition of Claim 61, wherein R22 is -OH
or -NR cR c.
65 . The pharmaceutical composition of Claim 61, wherein R23 is hydrogen, -CH2-N (N-CH3-D-glucamine); -CH2-NH-CH2CH2-NH-(CH2)9CH3;-CH2-NH-CH2CH2-NH-(CH2)11CH3; -CH2-NH-(CH2)5-COOH; or -CH2-N-(2-amino-2-deoxygluconic acid).
66. The pharmaceutical composition of Claim 61, wherein R24 is hydrogen and R26 is hydrogen or methyl.
67. The pharmaceutical composition of Claim 66, wherein R25 is alkyl or substituted alkyl.
68. The pharmaceutical composition of Claim 67, wherein R25 is isobutyl.
69. The pharmaceutical composition of Claim 68, wherein R27 is hydrogen, alkyl, substituted alkyl or -C(O)R d.
70. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically effective amount of a compound shown in any of Tables I, II, III, IV, V or VI, or a pharmaceutically-acceptable salt thereof.
71. A method of treating a mammal having a bacterial disease, the method comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition of Claim 36, 50 or 61.
CA2336445A 1998-12-23 1999-12-22 Glycopeptide derivatives and pharmaceutical compositions containing the same Expired - Lifetime CA2336445C (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US11372898P 1998-12-23 1998-12-23
US60/113,728 1998-12-23
US12931399P 1999-04-14 1999-04-14
US60/129,313 1999-04-14
US16402499P 1999-11-04 1999-11-04
US60/164,024 1999-11-04
US16997899P 1999-12-10 1999-12-10
US60/169,978 1999-12-10
PCT/US1999/030543 WO2000039156A1 (en) 1998-12-23 1999-12-22 Glycopeptide derivatives and pharmaceutical compositions containing the same

Publications (2)

Publication Number Publication Date
CA2336445A1 true CA2336445A1 (en) 2000-07-06
CA2336445C CA2336445C (en) 2011-07-19

Family

ID=27493926

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2336445A Expired - Lifetime CA2336445C (en) 1998-12-23 1999-12-22 Glycopeptide derivatives and pharmaceutical compositions containing the same

Country Status (23)

Country Link
US (9) US6392012B1 (en)
EP (1) EP1140993B1 (en)
JP (1) JP4362017B2 (en)
KR (1) KR100665204B1 (en)
CN (1) CN1249081C (en)
AT (1) ATE242783T1 (en)
AU (1) AU768204B2 (en)
BR (1) BRPI9914221B8 (en)
CA (1) CA2336445C (en)
CZ (1) CZ301184B6 (en)
DE (1) DE69908819T2 (en)
DK (1) DK1140993T3 (en)
ES (1) ES2201825T3 (en)
HK (1) HK1040721B (en)
HU (1) HU230190B1 (en)
IL (2) IL140093A0 (en)
NO (1) NO326066B1 (en)
NZ (1) NZ508594A (en)
PL (1) PL198311B1 (en)
PT (1) PT1140993E (en)
SI (1) SI1140993T1 (en)
WO (1) WO2000039156A1 (en)
ZA (1) ZA200007222B (en)

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU230190B1 (en) * 1998-12-23 2015-09-28 Theravance, Inc Glycopeptide derivatives and pharmaceutical compositions containing the same
US6699836B2 (en) * 1999-04-02 2004-03-02 The Trustees Of Princeton University Vancomycin analogs
AU4054900A (en) * 1999-04-02 2000-10-23 Advanced Medicine East, Inc. Desleucyl glycopeptide antibiotics and methods of making same
AU2001238020A1 (en) * 2000-02-04 2001-08-14 Advanced Medicine, Inc. Glycopeptide derivatives having antibiotic activity
SI1278549T1 (en) 2000-05-02 2009-04-30 Theravance Inc Composition containing a cyclodextrin and a glycopeptide antibiotic
AU2001259298A1 (en) 2000-05-02 2001-11-12 Advanced Medicine, Inc. Polyacid glycopeptide derivatives
KR100856479B1 (en) 2000-05-02 2008-09-04 세라밴스 인코포레이티드 Reductive alkylation process
ES2302733T3 (en) * 2000-06-22 2008-08-01 Theravance, Inc. CARBOXI-SACARIDS DERIVATIVES OF GLUCOPEPTIDE.
US6828299B2 (en) 2000-06-22 2004-12-07 Theravance, Inc. Polyhydroxy glycopeptide derivatives
UA75083C2 (en) * 2000-06-22 2006-03-15 Тераванс, Інк. Derivatives of glycopeptidephosphonates
US6872804B2 (en) 2000-06-22 2005-03-29 Theravance, Inc. Glycopeptide disulfide and thioester derivatives
US6905669B2 (en) * 2001-04-24 2005-06-14 Supergen, Inc. Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase
TWI312785B (en) * 2001-08-24 2009-08-01 Theravance Inc Process for preparing vancomycin derivatives
TWI275594B (en) 2001-08-24 2007-03-11 Theravance Inc Process for preparing vancomycin phosphonate derivatives
EP1295711B1 (en) 2001-09-19 2006-04-12 The Procter & Gamble Company A color printed laminated structure, absorbent article comprising the same and process for manufacturing the same
TWI335332B (en) * 2001-10-12 2011-01-01 Theravance Inc Cross-linked vancomycin-cephalosporin antibiotics
US20040033986A1 (en) 2002-05-17 2004-02-19 Protopopova Marina Nikolaevna Anti tubercular drug: compositions and methods
US7652039B2 (en) 2002-05-17 2010-01-26 Sequella, Inc. Methods of use and compositions for the diagnosis and treatment of infectious disease
TWI325323B (en) 2002-05-24 2010-06-01 Theravance Inc Cross-linked glycopeptide-cephalosporin antibiotics
WO2003106399A2 (en) 2002-06-17 2003-12-24 Theravance, Inc. PROCESS FOR PREPARING N-PROTECTED β-AMINO ALDEHYDE COMPOUNDS
AU2003248896B2 (en) * 2002-07-09 2010-04-22 Fasgen, Llc Methods of treating microbial infections in humans and animals
US20060074014A1 (en) * 2002-11-18 2006-04-06 Vicuron Pharmaceuticals Inc. Dalbavancin compositions for treatment of bacterial infections
US20050130909A1 (en) * 2002-11-18 2005-06-16 Luigi Colombo Dalbavancin compositions for treatment of bacterial infections
DE602004024393D1 (en) * 2003-05-23 2010-01-14 Theravance Inc CROSS-LINKED GLYCOPEPTIDE-CEPHALOSPORIN ANTIBIOTICS
WO2005005436A2 (en) * 2003-07-11 2005-01-20 Theravance, Inc. Cross-linked glycopeptide-cephalosporin antibiotics
DE102004055582A1 (en) * 2004-11-18 2006-05-24 Bayer Cropscience Ag N-heterocyclic-phthalic
EP1818340A4 (en) 2004-11-29 2009-02-25 Univ Nagoya Nat Univ Corp Glycopeptide antibiotic monomer derivatives
US8304597B2 (en) 2004-12-15 2012-11-06 The Procter And Gamble Company Method of using an absorbent article having a functional enhancement indicator
US7368422B2 (en) * 2005-02-28 2008-05-06 Novartis Vaccines And Diagnostics Inc. Semi-synthetic rearranged vancomycin/desmethyl-vancomycin-based glycopeptides with antibiotic activity
US20070185015A1 (en) * 2005-02-28 2007-08-09 Chiron Corporation and North China Pharmaceutical Corporation Semi-synthetic desmethyl-vancomycin-based glycopeptides with antibiotic activity
US7632918B2 (en) * 2005-02-28 2009-12-15 Novartis Vaccines And Diagnostics, Inc. Semi-synthetic glycopeptides with antibiotic activity
EP1933881B1 (en) 2005-09-22 2019-03-13 Medivas, LLC Solid polymer delivery compositions and methods for use thereof
EP1926780B1 (en) 2005-09-22 2013-08-14 Medivas, LLC Bis-( -amino)-diol-diester-containing poly(ester amide) and poly(ester urethane) compositions and methods of use
US20070173438A1 (en) * 2006-01-13 2007-07-26 The Scripps Research Institute [PSI[CH2NH]PG4] glycopeptide antibiotic analogs
TW200808818A (en) * 2006-05-26 2008-02-16 Shionogi & Co Glycopeptide antibiotic derivatives
JP5517153B2 (en) 2007-12-26 2014-06-11 塩野義製薬株式会社 Glycopeptide antibiotic glycosylated derivatives
CA2710602A1 (en) * 2007-12-26 2009-07-09 Lead Therapeutics, Inc. Novel semi-synthetic glycopeptides as antibacterial agents
CN102083862A (en) 2008-04-01 2011-06-01 康奈尔大学 Organo-soluble chitosan salts and chitosan-derived biomaterials prepared thereof
GB2465863A (en) * 2008-12-05 2010-06-09 Lead Therapeutics Inc Semi-synthetic heptapeptidic glycopeptides for the treatment of bacterial infections
CN101928330B (en) * 2009-06-26 2013-10-16 上海来益生物药物研究开发中心有限责任公司 New compound and application thereof
US20140171357A1 (en) * 2011-03-24 2014-06-19 Seachaid Pharmaceuticals, Inc. Vancomycin derivatives
WO2015040467A1 (en) * 2013-09-23 2015-03-26 Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Vancomycin-sugar conjugates and uses thereof
CA2972276A1 (en) * 2014-12-25 2016-06-30 Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Glycopeptides and uses thereof
KR20190031426A (en) * 2016-01-15 2019-03-26 함부르크대학교 Process for preparing laminocilized flavonoids
US10696698B2 (en) * 2016-01-28 2020-06-30 ACatechol, Inc. Surface primer compositions and methods of use
CN107325159A (en) * 2016-04-29 2017-11-07 中国科学院上海药物研究所 One class vancomycin derivatives, its preparation method, pharmaceutical composition and purposes
JP7210476B2 (en) * 2017-05-22 2023-01-23 インスメッド インコーポレイテッド Lipo-glycopeptide cleavable derivatives and uses thereof
CN107987131B (en) * 2017-11-16 2021-03-09 上海来益生物药物研究开发中心有限责任公司 Compound with anti-drug-resistance bacterial activity, preparation method and application thereof
CN108409837B (en) 2018-03-06 2021-09-24 上海来益生物药物研究开发中心有限责任公司 Glycopeptide compound with anti-drug resistance bacterial activity, preparation method and application thereof
NL2023883B1 (en) * 2019-09-24 2021-04-26 Univ Leiden Antibiotic compounds
CN111620931B (en) * 2020-06-12 2021-12-17 苏州博源医疗科技有限公司 Vancomycin derivative and preparation method and application thereof
CN114213284B (en) * 2022-01-04 2023-08-01 丽珠集团福州福兴医药有限公司 (9H-fluoren-9-yl) -decyl (2-oxo-ethyl) carbamic acid methyl ester and synthesis method thereof

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4497802A (en) 1983-10-21 1985-02-05 Eli Lilly And Company N-Acyl glycopeptide derivatives
GB8428619D0 (en) 1984-11-13 1984-12-19 Lepetit Spa Derivatives of antibiotic l 17046
US4914187A (en) 1984-11-13 1990-04-03 Gruppo Lepetit S.P.A Ester derivatives of antibiotic L 17046
US4698327A (en) 1985-04-25 1987-10-06 Eli Lilly And Company Novel glycopeptide derivatives
US4643987A (en) 1985-08-14 1987-02-17 Eli Lilly And Company Modified glycopeptides
US4639433A (en) 1985-08-14 1987-01-27 Eli Lilly And Company Glycopeptide derivatives
GB8704847D0 (en) 1987-03-02 1987-04-08 Lepetit Spa Substituted alkylamides of teicoplanin compounds
FR2632185B1 (en) * 1988-06-01 1992-05-22 Rhone Poulenc Chimie SILICA FOR TOOTHPASTE COMPOSITIONS COMPATIBLE IN PARTICULAR WITH ZINC
GB8817397D0 (en) 1988-07-21 1988-08-24 Lepetit Spa N15-alkyl & n15 n15-di-alkyl derivatives of teicoplanin antibiotics carrying functional groups on alkyl side chain
US5534420A (en) 1988-07-28 1996-07-09 Eli Lilly And Company Biotransformation of glycopeptide antibiotics
ES2083374T3 (en) 1988-12-27 1996-04-16 Lepetit Spa AMIDIC DERIVATIVES IN POSITION C63 OF 34-DES (ACETILGLUCOSAMINIL) -34-DESOXI-TEICOPLANINAS.
IE64155B1 (en) 1989-03-29 1995-07-12 Lepetit Spa New substituted alkylamide derivatives of teicoplanin
CA2031803C (en) 1989-12-13 2001-05-29 Ramakrishnan Nagarajan Improvements in or relating to glycopeptide deriveratives
AU647122B2 (en) 1990-05-28 1994-03-17 Gruppo Lepetit S.P.A. C63-amide derivatives of 34-de(acetylglucosaminyl)-34-deoxy- teicoplanin and their use as medicaments against bacteria resistant to glycopeptide antibiotics
WO1992017456A1 (en) 1991-03-26 1992-10-15 Fujisawa Pharmaceutical Co., Ltd. Amino acid derivative and salt thereof
US5750509A (en) 1991-07-29 1998-05-12 Gruppo Lepetit S.P.A. Amide derivatives of antibiotic A 40926
CA2109601C (en) 1991-07-29 2002-07-02 Adriano Malabarba Amide derivatives of antibiotic a 40926
AU703106B2 (en) 1994-01-28 1999-03-18 Eli Lilly And Company Glycopeptide antibiotic derivatives
US5840684A (en) 1994-01-28 1998-11-24 Eli Lilly And Company Glycopeptide antibiotic derivatives
IT1282586B1 (en) 1996-02-08 1998-03-31 Chemical And Biolog Ind PHARMACEUTICAL COMPOSITIONS FOR THE BIOLOGICAL TREATMENT OF INFECTIONS DUE TO STRAINS OF ENTEROCOCCUS FAECIUM RESISTANT TO
AU2341197A (en) 1996-03-21 1997-10-10 Intercardia, Inc. Solid phase lipoglycopeptide library, compositions and methods
JP4159110B2 (en) 1996-04-12 2008-10-01 イーライ・リリー・アンド・カンパニー Glycopeptide compound
AU2441697A (en) 1996-04-12 1997-11-07 Eli Lilly And Company Covalently-linked glycopeptide dimers
US6218505B1 (en) 1996-04-23 2001-04-17 Biosearch Italia S.P.A. Chemical process for preparing amide derivatives of antibiotic A 40926
US5919756A (en) 1996-06-28 1999-07-06 Eli Lilly And Company Amides
US5939382A (en) 1996-11-21 1999-08-17 Eli Lilly And Company Reducing agent for reductive alkylation of glycopeptide antibiotics
US5952466A (en) 1997-11-12 1999-09-14 Eli Lilly And Company Reductive alkylation of glycopeptide antibiotics
US5916873A (en) 1997-04-17 1999-06-29 Eli Lilly And Company Teicoplanin derivatives
US5952310A (en) 1997-05-20 1999-09-14 Eli Lilly And Company Glycopeptide hexapeptides
US5919771A (en) 1997-05-20 1999-07-06 Eli Lilly And Company Urea and thiourea derivatives of glycopeptides
US5977063A (en) 1997-05-20 1999-11-02 Eli Lilly And Company Alkylated hexapeptides
EP1060189A1 (en) 1998-02-20 2000-12-20 Advanced Medicine, Inc. Derivatives of glycopeptide antibacterial agents
US6518242B1 (en) * 1998-02-20 2003-02-11 Theravance, Inc. Derivatives of glycopeptide antibacterial agents
US6670446B1 (en) 1998-05-01 2003-12-30 Eli Lilly And Company N1 modified glycopeptides
NZ509165A (en) 1998-07-14 2003-08-29 Univ Princeton Glycopeptide antobiotics, combinatorial libraries of glycopeptide antibiotics and methods of producing same
HU230190B1 (en) * 1998-12-23 2015-09-28 Theravance, Inc Glycopeptide derivatives and pharmaceutical compositions containing the same
UA75083C2 (en) * 2000-06-22 2006-03-15 Тераванс, Інк. Derivatives of glycopeptidephosphonates
TWI325323B (en) * 2002-05-24 2010-06-01 Theravance Inc Cross-linked glycopeptide-cephalosporin antibiotics
WO2005005436A2 (en) * 2003-07-11 2005-01-20 Theravance, Inc. Cross-linked glycopeptide-cephalosporin antibiotics

Also Published As

Publication number Publication date
BR9914221A (en) 2001-06-26
BRPI9914221B8 (en) 2021-05-25
DK1140993T3 (en) 2003-10-06
US7723470B2 (en) 2010-05-25
CN1249081C (en) 2006-04-05
HK1040721B (en) 2003-10-17
US20040204346A1 (en) 2004-10-14
HUP0400887A2 (en) 2004-08-30
DE69908819T2 (en) 2004-05-06
EP1140993A1 (en) 2001-10-10
KR20010085857A (en) 2001-09-07
US6962970B2 (en) 2005-11-08
US20050239690A1 (en) 2005-10-27
AU3127300A (en) 2000-07-31
IL140093A0 (en) 2002-02-10
US20060241024A1 (en) 2006-10-26
PL198311B1 (en) 2008-06-30
NZ508594A (en) 2003-05-30
PT1140993E (en) 2003-10-31
CZ200122A3 (en) 2001-06-13
ATE242783T1 (en) 2003-06-15
US6444786B1 (en) 2002-09-03
SI1140993T1 (en) 2003-12-31
ES2201825T3 (en) 2004-03-16
WO2000039156A1 (en) 2000-07-06
EP1140993B1 (en) 2003-06-11
HUP0400887A3 (en) 2012-09-28
ZA200007222B (en) 2002-03-06
CZ301184B6 (en) 2009-12-02
US7351791B2 (en) 2008-04-01
NO20006323L (en) 2001-02-12
JP4362017B2 (en) 2009-11-11
BR9914221B1 (en) 2013-12-31
KR100665204B1 (en) 2007-01-04
US20090215982A1 (en) 2009-08-27
US8030445B2 (en) 2011-10-04
US20080103292A1 (en) 2008-05-01
NO20006323D0 (en) 2000-12-12
US20030060598A1 (en) 2003-03-27
IL140093A (en) 2006-06-11
JP2002533472A (en) 2002-10-08
HU230190B1 (en) 2015-09-28
HK1040721A1 (en) 2002-06-21
DE69908819D1 (en) 2003-07-17
CA2336445C (en) 2011-07-19
PL348451A1 (en) 2002-05-20
US7101964B2 (en) 2006-09-05
AU768204B2 (en) 2003-12-04
NO326066B1 (en) 2008-09-08
US6392012B1 (en) 2002-05-21
US6455669B1 (en) 2002-09-24
CN1315961A (en) 2001-10-03
US6949681B2 (en) 2005-09-27

Similar Documents

Publication Publication Date Title
CA2336445A1 (en) Glycopeptide derivatives and pharmaceutical compositions containing the same
CA2411590A1 (en) Glycopeptide phosphonate derivatives
KR940007022A (en) Piperidine derivatives, their use in the preparation and treatment thereof
KR930019637A (en) Imidazole derivatives having biphenylsulfonylurea or biphenylsulfonylurethane side chains, preparation method and use thereof
CA2408008A1 (en) Pharmaceutical compositions containing a glycopeptide antibiotic and a cyclodextrin
CA2197672A1 (en) Tetrahydrofuran antifungals
ES514240A0 (en) A PROCEDURE FOR THE PREPARATION OF NEW 2-CARBAMIMIDOIL-1-, CARBADESTIAPEN-2-EN-3-CARBOXYLATED ACID DERIVATIVES.
KR900015729A (en) Excitatory amino acid antagonists
KR960701881A (en) Ureido derivatives of naphtha1enephosphonic acids and process for their preparation
CA2491802A1 (en) Novel compounds, pharmaceutical compositions containing same, and methods of use for same
ATE239471T1 (en) COMBINATION OF AN ANGIOTENSIN-II ANTAGONISTIC BENZIMIDAZOLE WITH A DIURETIC
KR870700067A (en) Pyrido (2,3-d) -pyrimidine derivatives
DK157545C (en) METHOD OF ANALOGUE FOR THE PREPARATION OF 4-PHENYL-1-HYDROXYALKYLIMIDAZOLD DERIVATIVES OR PHARMACEUTICAL ACCEPTABLE ACID ADDITION SALTS.
GB1325970A (en) Pharmaceutical compositions
KR920017659A (en) Use of phosphatidylserine and its derivatives in degenerative lesions associated with immune dysfunction
KR900004658A (en) Disubstituted benzylamine, preparation method thereof, use thereof as medicament and synthesis agent thereof
RU2003134629A (en) CEPHEMA COMPOUNDS
KR890016017A (en) Substituted 1- (1H-imidazol-4-yl) alkyl-benzamide
KR890013028A (en) Cephalosporin derivatives and their preparation
KR900014396A (en) Thieno-triazolo-diazepine derivatives, methods for their preparation and therapeutic compositions containing them
DE69729104D1 (en) PHARMACEUTICAL COMPOSITIONS CONTAINING TYRPHOSTINE
EP0210753A3 (en) Anti-tumor medicament
KR920000715A (en) New N-benzyl-N1-phenyl-and-phenalkyl-thioureas
CA2569993A1 (en) Novel antiviral macrocycle derivatives and metal complexes, incorporating bridged macrocycles
RU93005114A (en) FOAM CONNECTIONS AND PHARMACEUTICAL COMPOSITION ON THEIR BASIS

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20191223